Clinical Symptoms Of Attention Deficit Hyperactivity Disorder Research Articles

36 Reactivity to Loss and Its Relationship to Clinical Symptoms of ADHD in Adults

Objective:Individuals with attention-deficit/hyperactivity disorder (ADHD) exhibit deficits in reward-based learning, which have important implications for behavioral regulation. Prior research has shown that these individuals show altered patterns of risky decision-making, which may be partially explained as a function of dysfunctional reactivity to rewards and punishments. However, research findings on the relationships between ADHD and punishment sensitivity have been mixed. The current study used the Balloon Analog Risk Task (BART) to examine risky decision-making in adults with and without ADHD, with a particular interest in characterizing the manner in which participants react to loss.Participants and Methods:612 individuals (Mage = 31.04, SDage = 78.77; 329 females, 283 males) were recruited through the UCLA Consortium for Neuropsychiatric Phenomics (CNP). All participants were administered the Structured Clinical Interview for DSM-IV-TR (SCID-IV), which provided diagnoses used for group comparisons between adults with ADHD (n = 35) and healthy controls (n = 577). A computerized BART paradigm was used to examine impulsivity and risky decision-making, while participants also completed the Barratt Impulsiveness Scale (BIS-11), and ADHD participants completed the Adult Self-Report Scale-V1.1 (ASRS-V1.1). The BART presented two colors of balloons with differing probabilities of exploding, and participants were incentivized to pump the balloons as many times as possible without causing them to explode. The primary endpoint was "mean adjusted pumps", determined as mean across trials of the number of pumps on trials that did not end in explosion. An index of reactivity to loss was calculated as the difference between the mean adjusted pumps following an explosion and the mean adjusted pumps following trials in which the balloon did not explode.Results:The ADHD and control groups did not differ on mean adjusted pumps across trials, but they did differ in their reactivity to explosion of balloons that followed the most pumps, incurring the greatest level of loss (F(1, 551) = 7.1, p < 0.01). Interestingly, ADHD participants showed a greater reactivity to loss on these balloons than controls (p < 0.05), indicating that they reduced their number of pumps following balloon explosions more than controls. For participants as a whole, there were small correlations between loss reactivity and scales of everyday impulsivity on the BIS-II (ps < 0.05). For ADHD participants, loss reactivity was unrelated to symptoms of inattention but was significantly correlated with symptoms of hyperactivity/impulsivity (p = 0.01) and total ADHD symptoms (p < 0.05) on the ASRS-V1.1.Conclusions:In the context of a risky decision-making task, adults with ADHD showed greater reactivity to loss than controls, despite showing comparable patterns of overall performance during the BART. The magnitude of behavioral adjustment following loss was correlated with symptoms of hyperactivity/impulsivity in adults with ADHD, suggesting that loss sensitivity is clinically related to impulsive behavior in everyday life. These findings help to expand our understanding of motivational processing in ADHD and suggest new insight into the ways in which everyday symptoms of ADHD are related to sensitivity to losses and punishments.

Correlation research of susceptibility single nucleotide polymorphisms and the severity of clinical symptoms in attention deficit hyperactivity disorder.

ObjectiveTo analyze the correlation between susceptibility single nucleotide polymorphisms (SNPs) and the severity of clinical symptoms in children with attention deficit hyperactivity disorder (ADHD), so as to supplement the clinical significance of gene polymorphism and increase our understanding of the association between genetic mutations and ADHD phenotypes.Methods193 children with ADHD were included in our study from February 2017 to February 2020 in the Children’s ADHD Clinic of the author’s medical institution. 23 ADHD susceptibility SNPs were selected based on the literature, and multiple polymerase chain reaction (PCR) targeted capture sequencing technology was used for gene analysis. A series of ADHD-related questionnaires were used to reflect the severity of the disease, and the correlation between the SNPs of specific sites and the severity of clinical symptoms was evaluated. R software was used to search for independent risk factors by multivariate logistic regression and the “corplot” package was used for correlation analysis.ResultsAmong the 23 SNP loci of ADHD children, no mutation was detected in 6 loci, and 2 loci did not conform to Hardy-Weinberg equilibrium. Of the remaining 15 loci, there were 9 SNPs, rs2652511 (SLC6A3 locus), rs1410739 (OBI1-AS1 locus), rs3768046 (TIE1 locus), rs223508 (MANBA locus), rs2906457 (ST3GAL3 locus), rs4916723 (LINC00461 locus), rs9677504 (SPAG16 locus), rs1427829 (intron) and rs11210892 (intron), correlated with the severity of clinical symptoms of ADHD. Specifically, rs1410739 (OBI1-AS1 locus) was found to simultaneously affect conduct problems, control ability and abstract thinking ability of children with ADHD.ConclusionThere were 9 SNPs significantly correlated with the severity of clinical symptoms in children with ADHD, and the rs1410739 (OBI1-AS1 locus) may provide a new direction for ADHD research. Our study builds on previous susceptibility research and further investigates the impact of a single SNP on the severity of clinical symptoms of ADHD. This can help improve the diagnosis, prognosis and treatment of ADHD.

Enhancing neural markers of attention in children with ADHD using a digital therapeutic

Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition characterized by diminished attentional control. Critically, these difficulties are related to negative consequences in real-life functioning both during development and into adulthood. There is now growing evidence that modulating the underlying neural circuits related to attention can improve behavior and brain function in children with ADHD. We have previously shown that game-based digital therapeutics targeting a key neural marker of attention–midline frontal theta (MFT)–yield positive effects on attentional control in several populations. However, the effects of such digital therapeutics in children with ADHD and no other comorbidities has not been yet examined. To address this gap, we assessed a sample of 25 children with ADHD (8–12 years old) on neural, behavioral, and clinical metrics of attention before and after a 4-week at-home intervention on an iPad targeting MFT circuitry. We found that children showed enhancements on a neural measure of attention (MFT power), as well as on objective behavioral measures of attention and parent reports of clinical ADHD symptoms. Importantly, we observed relationships between the neural and behavioral cognitive improvements, demonstrating that those children who showed the largest intervention-related neural gains were also those that improved the most on the behavioral tasks indexing attention. These findings provide support for using targeted, digital therapeutics to enhance multiple features of attentional control in children with ADHD.Study registration: ClinicalTrials.gov registry (NCT03844269) https://clinicaltrials.gov/ct2/show/NCT03844269.

Perceptual-Motor Skills Reconstruction Program Improves Executive Functions in Children with Attention-Deficit/Hyperactivity Disorder

Objective: Many children suffering from attention-deficit/hyperactivity disorder (ADHD) show problems in executive functions (EF), which reflect neuronal pathways from perception to controlled action. Treatment approaches that improve executive functions may prevent a negative cycle of failures in students. Hence, this research aims to study the efficacy of the perceptual-motor skills reconstruction program on EF in children with ADHD while considering cognitive flexibility, abstract verbal skills, response inhibition, and working memory. Also, its effect on clinical ADHD symptoms should be considered. Method: The research design included pretest, posttest, and a follow-up after six months. The sample included third-grade school children with ADHD (50 students, aged 8–10 years, boys and girls) who were referred to the Child Psychology Clinic, Iran, Mashhad 2018–2019. After clinical assessment for ADHD, children were randomly assigned to an experimental (n = 25) and a waiting control (n = 25) group. The experimental group received the perceptual-motor skills reconstruction program for 16 sessions (three times per week, i.e., five weeks and one session in the sixth week). Delis–Kaplan executive function system (D-KEFS) was applied at three measurement points (M1–3) in order to test for changes over time. Results: Data analysis (analysis of covariance (ANCOVA) with post-hoc-testing) showed that there was a significantly better performance of experimental versus waiting control group at posttest (M2) and follow-up (M3) for cognitive flexibility (t(24) = 4.9, df = 14, p < 0.0001), abstract verbal skills (t(24) = 3.5, df = 14, p < 0.004), response inhibition (t(24) = 7.54, df = 14, p < 0.0001) and working memory (t(24) = 12.69, df = 14, p < 0.004). Further, Conners-Scales-Score improved for the experimental group. Conclusions: Training with perceptual-motor skills reconstruction program clearly improved the trained variables (i.e., cognitive flexibility, abstract verbal skills, response inhibition, and working memory) and clinical symptoms of the children with ADHD. The obtained training may lead in practice to better preconditions for successfully handling daily tasks at school and in society.

Attention-deficit/hyperactivity disorder and behavioural planning deficiencies in South African primary school children.

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is defined as a cognitive or behavioural developmental disorder. Inattentiveness, overactivity and impulsivity are regarded as the main clinical symptoms of ADHD. These symptoms may occur together or separately resulting in three recognised presentations: predominantly inattentive, predominantly hyperactive–impulsive and combined presentations.AimThis study investigated deficiencies in behavioural planning in South African primary school children with and without ADHD.SettingTzaneen area in Limpopo province, South Africa.MethodsA total of 156 children (78 with ADHD and 78 matched controls without ADHD) of both genders, who were medication naïve and aged 6–15 years, participated in the study. The performance of the two groups was compared on a test of planning and problem-solving, the Tower of London (ToL) task. The results were analysed as a function of gender, age and ADHD presentation.ResultsChildren with ADHD especially ADHD-PI and ADHD-C used significantly more moves and took a longer time to complete the task than the controls (p < 0.001). There were no significant differences in the number of moves and time taken by the predominantly hyperactive-impulsive presentations of ADHD when compared to the controls. Gender and age did not influence the performance.ConclusionThe results showed that children with ADHD showed significantly more deficits mainly the ADHD-PI and ADHD-C presentations, which indicates that inattention is mainly responsible for deficiencies in behaviour planning. The ADHD-HI presentations and the control group were not affected.

Novel plasma metabolite markers of attention-deficit/hyperactivity disorder identified using high-performance chemical isotope labelling-based liquid chromatography-mass spectrometry

Objectives Metabolites are the intermediate and final products of biological processes and ultimately reflect the responses of these processes to genetic regulation and environmental perturbations, including those involved in attention deficit/hyperactivity disorder (ADHD). Methods We identified a quantitative profile of plasma metabolites in 58 ADHD patients (mean age 9.0 years, 77.6% males) and 38 healthy control subjects (mean age 10.2 years, 55.3% males) using the high-performance chemical isotope labelling (CIL)-based liquid chromatography-mass spectrometry (LC-MS). Using a volcano plot and orthogonal projections to latent structure-discriminant analysis (OPLS-DA), we determined nine metabolites with differentially expressed levels in ADHD plasma samples. Results Compared to the control group, the plasma levels of guanosine, O-phosphoethanolamine, phenyl-leucine, hypoxanthine, 4-aminohippuric acid, 5-hydroxylysine, and L-cystine appeared increased in the ADHD patients, whilegentisic acid and tryptophyl-phenylalanine were down-regulated in the patients with ADHD. We found that the plasma levels of all nine metabolites were able to discriminate the ADHD group from the control group. Levels of O-phosphoethanolamine, 4-aminohippuric acid, 5-hydroxylysine, L-cystine, tryptophyl-phenylalanine, and gentisic acid were significantly correlated with clinical ADHD symptoms. Conclusions This study is the first to use the CIL-based LC-MS to profile ADHD plasma metabolites, and we identified nine novel metabolite biomarkers of ADHD.

Pilot Study: An Ocular Biomarker for Diagnosis of Attention Deficit Hyperactivity Disorder.

ObjectiveBiomarkers of attention deficit hyperactivity disorder (ADHD) are crucial for early diagnosis and intervention, in which the identification of biomarkers in other areas of the body that represent the immature brain of children with ADHD is necessary. The present study aimed to find biomarkers of ADHD in the retina and assessed the relationship between macular thickness of the retina and cortical thickness of the brain in children with ADHD. MethodsTwelve children with ADHD and 13 control children were recruited for the study. To find ocular markers of ADHD, we investigated the correlation between clinical symptoms of ADHD assessed with the Korean ADHD Rating Scale (K-ARS), cortical thickness of the brain, and macular thickness measured with the mean thickness from the Early Treatment Diabetic Retinopathy Study (ETDRS). ResultsChildren with ADHD showed increased macular thicknesses quantified as an ETDRS ring in both eyes, compared to control subjects. Moreover, the right inner ETDRS ring had a positive correlation with K-ARS scores. The ADHD group had an increased ratio of thickness of the right frontal lobe to that of the parietal cortex, compared with the control group. There were positive correlations between the means of the inner ETDRS ring (right) and the left paracentral/right isthmus cingulate thicknesses in the control group. However, there were negative correlations between the means of the inner ETDRS ring (right) and the left frontal pole/right pars triangularis thicknesses in the ADHD group. The results of both groups were at the uncorrected level. ConclusionThe different patterns of macular thickness might represent the immature cortical thickness of the brain in children with ADHD.

Transcranial direct current stimulation in attention-deficit hyperactivity disorder: A meta-analysis of neuropsychological deficits.

Transcranial direct current stimulation (tDCS) is a promising method for altering cortical excitability with clinical implications in neuropsychiatric diseases. Its application in neurodevelopmental disorders especially attention-deficit hyperactivity disorder (ADHD), is in early stage and promising but its effectiveness has not been systematically examined yet. We conducted a meta-analysis on the effectiveness of tDCS on the most studied neuropsychological symptoms of ADHD, which is the first reported meta-analysis of tDCS studies on ADHD. Data from 10 randomized controlled studies (including 11 separate experiments) targeting inhibitory control, and/or working memory (WM) in ADHD were included. Results show that overall tDCS significantly improved inhibitory control. Sub-analyses further show that dorsolateral prefrontal cortex (dlPFC) (but not right inferior frontal gyrus) tDCS and anodal (but not cathodal) tDCS significantly improved inhibitory control with a small effect size. Anodal dlPFC-tDCS had the largest significant effect on inhibitory control with a small-to-medium effect size. Additionally, a significant improving effect of tDCS on inhibitory control accuracy (but not response time) and WM speed (but not accuracy) were found. Overall, this meta-analysis supports a beneficial effect of tDCS on inhibitory control and WM in ADHD with a small-to-medium effect size. TDCS seems to be a promising method for improving neuropsychological and cognitive deficits in ADHD. However, there might be a dissociation between neuropsychological deficits and clinical symptoms of ADHD and therefore, the significance of this meta-analysis for clinical purposes is limited. Future studies should systematically evaluate the role of inter-individual factors (i.e., ADHD subtype, types of the deficit) and stimulation parameters (i.e., site, polarity, intensity, duration, repetition rate) on tDCS efficacy in ADHD population and examine whether benefits are long-term.

Predicting clinical symptoms of attention deficit hyperactivity disorder based on temporal patterns between and within intrinsic connectivity networks

Attention deficit hyperactivity disorder (ADHD) is a common brain disorder with high prevalence in school-age children. Previously developed machine learning-based methods have discriminated patients with ADHD from normal controls by providing label information of the disease for individuals. Inattention and impulsivity are the two most significant clinical symptoms of ADHD. However, predicting clinical symptoms (i.e., inattention and impulsivity) is a challenging task based on neuroimaging data. The goal of this study is twofold: to build predictive models for clinical symptoms of ADHD based on resting-state fMRI and to mine brain networks for predictive patterns of inattention and impulsivity. To achieve this goal, a cohort of 74 boys with ADHD and a cohort of 69 age-matched normal controls were recruited from the ADHD-200 Consortium. Both structural and resting-state fMRI images were obtained for each participant. Temporal patterns between and within intrinsic connectivity networks (ICNs) were applied as raw features in the predictive models. Specifically, sample entropy was taken asan intra-ICN feature, and phase synchronization (PS) was used asan inter-ICN feature. The predictive models were based on the least absolute shrinkage and selectionator operator (LASSO) algorithm. The performance of the predictive model for inattention is r=0.79 (p<10−8), and the performance of the predictive model for impulsivity is r=0.48 (p<10−8). The ICN-related predictive patterns may provide valuable information for investigating the brain network mechanisms of ADHD. In summary, the predictive models for clinical symptoms could be beneficial for personalizing ADHD medications.

Predictors of Nicotine Dependence in Adolescents: Symptoms of Bipolar Disorder and Attention-Deficit/Hyperactivity Disorder.

Bipolar disorder (BD) and attention-deficit/hyperactivity disorder (ADHD) have been associated with the use of cigarettes, but little is known about the impact of the subthreshold symptoms of BD or ADHD on the course of nicotine dependence. Identifying the links is essential for elucidating the pathway and supporting the development of nicotine prevention strategies for adolescents. Participants (n = 3322) aged 15-17 years completed the Chinese version of the ADHD Self-Report Scale and the Mood Disorder Questionnaire. The modified Fagerström Tolerance Questionnaire was completed to measure their nicotine use or dependence. Mediation analyses were performed to explore the relationship of two predictors. The prevalence rates of cigarette smoking and nicotine dependence in this study were 14.4% and 2.3%, respectively. Male gender (odds ratio [OR] 2.30; 95% confidence interval [CI] 1.60-3.30), subclinical symptoms of ADHD (OR 1.34; 95% CI 1.04-1.71), clinical symptoms of ADHD (OR 1.69; 95% CI 1.08-2.66), and symptoms of BD (OR 1.59; 95% CI1.09 to 2.32) were associated with nicotine use. Male gender (OR 4.60; 95% CI 1.41-14.98) and symptoms of BD (OR 6.14; 95% CI 3.37-11.18), but not symptoms of ADHD, were associated with nicotine dependence. In mediation analyses, we found that the effect of ADHD symptoms was no longer significant after controlling for symptoms of BD, and the mediation ratio (PM) was 0.39. Our findings suggest that mood disturbances other than symptoms of ADHD are more likely to be a key predictor of nicotine dependence among adolescents. The conclusions may improve our understanding of the course of nicotine dependence and help to promote potential health policy for nicotine control among youths.

A Randomized Trial of Comparing the Efficacy of Two Neurofeedback Protocols for Treatment of Clinical and Cognitive Symptoms of ADHD: Theta Suppression/Beta Enhancement and Theta Suppression/Alpha Enhancement.

Introduction. Neurofeedback (NF) is an adjuvant or alternative therapy for children with Attention Deficit Hyperactivity Disorder (ADHD). This study intended to compare the efficacy of two different NF protocols on clinical and cognitive symptoms of ADHD. Materials and Methods. In this clinical trial, sixty children with ADHD aged 7 to 10 years old were randomly grouped to receive two different NF treatments (theta suppression/beta enhancement protocol and theta suppression/alpha enhancement protocol). Clinical and cognitive assessments were conducted prior to and following the treatment and also after an eight-week follow-up. Results. Both protocols alleviated the symptoms of ADHD in general (p < 0.001), hyperactivity (p < 0.001), inattention (p < 0.001), and omission errors (p < 0.001); however, they did not affect the oppositional and impulsive scales nor commission errors. These effects were maintained after an eight-week intervention-free period. The only significant difference between the two NF protocols was that high-frequency alpha enhancement protocol performed better in suppressing omission errors (p < 0.001). Conclusion. The two NF protocols with theta suppression/beta enhancement and theta suppression/alpha enhancement have considerable and comparable effect on clinical symptoms of ADHD. Alpha enhancement protocol was more effective in suppressing omission errors.

WITHDRAWN: Immediate-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults.

Background Symptoms of attention deficit hyperactivity disorder (ADHD), diagnosed mainly in children, often persist into adulthood. Adults in this group have a rate of other psychiatric problems and functional difficulties in a number of key areas such as academic achievement, interpersonal relationships, and employment. Although the usefulness of immediate-release methylphenidate in children has been extensively studied, studies in adults, which are few, demonstrate varying results. Objectives To evaluate the efficacy and tolerability of immediate-release methylphenidate versus placebo in the treatment of adults with ADHD. Search methods We searched the following databases in November 2013: CENTRAL, Ovid MEDLINE, EMBASE, PsycINFO, Database of Abstracts of Reviews of Effects (DARE), and two trials registers. Biosis was searched in December 2013. We inspected references of all relevant papers to identify more studies and contacted authors of recently published trials. Selection criteria We included all randomized trials comparing immediate-release methylphenidate versus placebo in participants aged 18 years or older with ADHD. We excluded trials conducted on subpopulations of adults with ADHD such as adults with both ADHD and substance dependence. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed trial risk of bias. We contacted authors of trials to ask for additional and missing data. For dichotomous outcomes, we calculated risk ratios (RRs) and 95% confidence intervals (CIs). For continuous outcomes, we calculated mean differences (MDs) or standardized mean differences (SMDs) with 95% CIs. Main results Results from the 11 randomized controlled trials (474 participants, counting participants from cross-over studies as a single arm, and counting both arms from parallel studies) included in the review demonstrated improvement in core clinical ADHD symptoms of hyperactivity, impulsivity, and inattentiveness, and overall improvement. We were able to pool results from 10 studies, which included 466 participants. Most included studies were judged to have unclear risk of bias for most categories. However, as all studies were randomized, double-blind, and placebo-controlled and, in general, did not contain factors that significantly decreased the quality of the body of evidence, the quality of evidence was assessed as high for most outcomes according to the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. For one outcome—inattentiveness—most information came from studies at unclear risk of bias, and so the quality of evidence for this outcome was judged as moderate. Results are given as SMD for each of the core clinical symptoms of ADHD. In all cases, participant numbers were calculated by counting participants in a single arm from cross-over studies and in both arms from parallel studies. The SMD for the outcome of hyperactivity was -0.60 (95% CI -1.11 to -0.09, 6 studies, number of participants (n) = 245, high-quality evidence) in favor of immediate-release methylphenidate; the SMD for impulsivity was -0.62 (95% CI -1.08 to -0.17, 5 studies, n = 207, high-quality evidence) in favor of immediate-release methylphenidate; and the SMD for inattentiveness was -0.66 (95% CI -1.02 to -0.30, 7 studies, n = 391, moderate-quality evidence) in favor of immediate-release methylphenidate. Moderate to extreme statistical heterogeneity was detected for all outcomes. Subgroup analysis comparing versus low doses did not indicate that higher doses of immediate-release methylphenidate were associated with greater efficacy. For overall change, the SMD was -0.72 (95% CI -1.12 to -0.32, 9 studies, n = 455, high-quality evidence) in favor of immediate-release methylphenidate. The effects of immediate-release methylphenidate on anxiety and depression as parameters of general changes in mental state were equivocal. Some trials reported reduction in depression and anxiety, others detailed no change, and still others described an increase in depressive and anxious symptoms. The most common adverse effect was loss of appetite, in some cases with weight loss. Although no study reported either of these effects as problematic or severe, the included studies were of short duration; thus clinical significance could not be properly assessed. Five studies reported changes in systolic or diastolic blood pressure, and three reported increases in heart rate. None of these results were judged to present cause for concern. No study reported clinically significant adverse effects—cardiovascular or other. Three studies did not mention adverse effects. We were unable to determine whether adverse effects were not discussed by study authors because none occurred, or because no data on adverse effects were collected. Authors' conclusions Data from randomized controlled trials suggest that immediate-release methylphenidate is efficacious for treating adults with ADHD with symptoms of hyperactivity, impulsivity, and inattentiveness, and for improving their overall clinical condition. Trial data suggest that adverse effects from immediate-release methylphenidate for adults with ADHD are not of serious clinical significance, although this conclusion may be limited, certainly in the case of weight loss, by the short duration of published studies.

Effects of methylphenidate on body index and physical fitness in Korean children with attention deficit hyperactivity disorder.

The side effects of methylphenidate (MPH) on growth remain a controversial concern. This study aimed to investigate the effect of MPH on clinical symptoms, growth, and physical fitness in Korean children. Fifty male children with attention deficit hyperactivity disorder (ADHD) treated with methylphenidate (MPH-ADHD), 69 MPH-naïve male children with ADHD (Naïve-ADHD), and 60 age-matched and sex-matched healthy control subjects were recruited. Intelligence quotient (IQ), clinical symptoms of ADHD, body index (height, weight, and body mass index [BMI]), and physical fitness (muscular strength, endurance, flexibility, agility, speed, and balance) were assessed. Total IQ and performance IQ scores were significantly different among the three groups, as were mean Korean Attention Deficit Hyperactivity Disorder (K-ARS)-total, K-ARS-inattention, and K-ARS-hyperactivity scores. There was no significant difference in height, weight, or BMI among the three groups. There were significant differences in skill-related fitness scores for balance (healthy controls > MPH-ADHD > Naïve-ADHD) and agility shuttle test time (healthy controls < MPH-ADHD < Naïve-ADHD). Our findings support the effectiveness of MPH treatment for improving IQ, attention, and balance and agility measures of skill-related fitness in Korean children with ADHD. MPH was not associated with growth delays in height, weight, and BMI.

A randomized controlled clinical trial of real-time functional magnetic resonance imaging neurofeedback for adolescents with attention deficit hyperactivity disorder (ADHD)

A randomized controlled clinical trial of real-time functional magnetic resonance imaging neurofeedback for adolescents with attention deficit hyperactivity disorder (ADHD)

Behavioral effects of neurofeedback in adolescents with ADHD: a randomized controlled trial.

Neurofeedback has been proposed as a potentially effective intervention for reducing Attention Deficit Hyperactivity Disorder (ADHD) symptoms. However, it remains unclear whether neurofeedback is of additional value to treatment as usual (TAU) for adolescents with clinical ADHD symptoms. Using a multicenter parallel-randomized controlled trial design, adolescents with ADHD symptoms were randomized to receive either a combination of TAU and neurofeedback (NFB+TAU, n=45) or TAU-only (n=26). Randomization was computer generated and stratified for age group (ages 12 through 16, 16 through 20, 20 through 24). Neurofeedback treatment consisted of approximately 37 sessions of theta/sensorimotor rhythm (SMR)-training on the vertex (Cz). Primary behavioral outcome measures included the ADHD-rating scale, Youth Self Report, and Child Behavior Checklist all assessed pre- and post-intervention. Behavioral problems decreased equally for both groups with medium to large effect sizes, rangeof partial η2=0.08-0.31, p<0.05. Hence, the combination of NFB+TAU was not more effective than TAU-only on the behavioral outcome measures. In addition, reported adverse effects were similar for both groups. On behavioral outcome measures, the combination of neurofeedback and TAU was as effective as TAU-only for adolescents with ADHD symptoms. Considering the absence of additional behavioral effects in the current study, in combination with the limited knowledge of specific treatment effects, it is questionable whether theta/SMR neurofeedback for adolescents with ADHD and comorbid disorders in clinical practice should be used. Further research is warranted to investigate possible working mechanisms and (long-term) specific treatment effects of neurofeedback.

Immediate-release methylphenidate for attention deficit hyperactivity disorder (ADHD) in adults.

Symptoms of attention deficit hyperactivity disorder (ADHD), diagnosed mainly in children, often persist into adulthood. Adults in this group have a high rate of other psychiatric problems and functional difficulties in a number of key areas such as academic achievement, interpersonal relationships, and employment. Although the usefulness of immediate-release methylphenidate in children has been extensively studied, studies in adults, which are few, demonstrate varying results. To evaluate the efficacy and tolerability of immediate-release methylphenidate versus placebo in the treatment of adults with ADHD. We searched the following databases in November 2013: CENTRAL, Ovid MEDLINE, EMBASE, PsycINFO, Database of Abstracts of Reviews of Effects (DARE), and two trials registers. Biosis was searched in December 2013. We inspected references of all relevant papers to identify more studies and contacted authors of recently published trials. We included all randomized trials comparing immediate-release methylphenidate versus placebo in participants aged 18 years or older with ADHD. We excluded trials conducted on subpopulations of adults with ADHD such as adults with both ADHD and substance dependence. Two review authors independently selected trials, extracted data, and assessed trial risk of bias. We contacted authors of trials to ask for additional and missing data. For dichotomous outcomes, we calculated risk ratios (RRs) and 95% confidence intervals (CIs). For continuous outcomes, we calculated mean differences (MDs) or standardized mean differences (SMDs) with 95% CIs. Results from the 11 randomized controlled trials (474 participants, counting participants from cross-over studies as a single arm, and counting both arms from parallel studies) included in the review demonstrated improvement in core clinical ADHD symptoms of hyperactivity, impulsivity, and inattentiveness, and overall improvement. We were able to pool results from 10 studies, which included 466 participants.Most included studies were judged to have unclear risk of bias for most categories. However, as all studies were randomized, double-blind, and placebo-controlled and, in general, did not contain factors that significantly decreased the quality of the body of evidence, the quality of evidence was assessed as "high" for most outcomes according to the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. For one outcome-inattentiveness-most information came from studies at unclear risk of bias, and so the quality of evidence for this outcome was judged as "moderate."Results are given as SMD for each of the core clinical symptoms of ADHD. In all cases, participant numbers were calculated by counting participants in a single arm from cross-over studies and in both arms from parallel studies. The SMD for the outcome of hyperactivity was -0.60 (95% CI -1.11 to -0.09, 6 studies, number of participants (n) = 245, high-quality evidence) in favor of immediate-release methylphenidate; the SMD for impulsivity was -0.62 (95% CI -1.08 to -0.17, 5 studies, n = 207, high-quality evidence) in favor of immediate-release methylphenidate; and the SMD for inattentiveness was -0.66 (95% CI -1.02 to -0.30, 7 studies, n = 391, moderate-quality evidence) in favor of immediate-release methylphenidate. Moderate to extreme statistical heterogeneity was detected for all outcomes. Subgroup analysis comparing high versus low doses did not indicate that higher doses of immediate-release methylphenidate were associated with greater efficacy.For overall change, the SMD was -0.72 (95% CI -1.12 to -0.32, 9 studies, n = 455, high-quality evidence) in favor of immediate-release methylphenidate.The effects of immediate-release methylphenidate on anxiety and depression as parameters of general changes in mental state were equivocal. Some trials reported reduction in depression and anxiety, others detailed no change, and still others described an increase in depressive and anxious symptoms.The most common adverse effect was loss of appetite, in some cases with weight loss. Although no study reported either of these effects as problematic or severe, the included studies were of short duration; thus clinical significance could not be properly assessed. Five studies reported changes in systolic or diastolic blood pressure, and three reported increases in heart rate. None of these results were judged to present cause for concern. No study reported clinically significant adverse effects-cardiovascular or other. Three studies did not mention adverse effects. We were unable to determine whether adverse effects were not discussed by study authors because none occurred, or because no data on adverse effects were collected. Data from randomized controlled trials suggest that immediate-release methylphenidate is efficacious for treating adults with ADHD with symptoms of hyperactivity, impulsivity, and inattentiveness, and for improving their overall clinical condition. Trial data suggest that adverse effects from immediate-release methylphenidate for adults with ADHD are not of serious clinical significance, although this conclusion may be limited, certainly in the case of weight loss, by the short duration of published studies.

Impairment in Young Preschool Children with Symptoms of Attention-Deficit/Hyperactivity Disorder and Co-occurring Oppositional Defiant Disorder and Conduct Disorder

Abstract Background: We have limited knowledge of the impact of attention-deficit/hyperactivity disorder (ADHD) symptoms on the daily functioning of young preschool children. Objective: This study investigated the level of impairment related to symptoms of ADHD in different functional domains. It also addressed how impairment caused by ADHD was related to ADHD subtype, symptom load, gender, and the co-occurrence of oppositional defiant disorder, conduct disorder, or both. Method: Participating children (N = 807) who were 3.5 years old were recruited from a population-based sample included in The Norwegian Mother and Child Cohort Study. Children who scored above the 90th percentile for ADHD symptoms were included in the present sample. The assessment of the symptoms and functional impairment described in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, text revision, was based on parental ratings and the semi-structured psychiatric interview entitled “The Preschool Age Psychiatric Assessment.” Results: Added burden and discord within family relationships were the areas that were most severely affected. All domain scores were strongly intercorrelated, and they were added to each child’s total score. Children with symptoms of ADHD, inattentive type (mean [M], 3.5; standard deviation [SD], 3.4), or ADHD, hyperactive/impulsive type (M, 2.9; SD, 2.7), were significantly less impaired than children with symptoms of ADHD, combined type (M = 6.4; SD = 3.8; p ` .001). Furthermore, co-occurring oppositional defiant disorder was associated with higher impairment scores (M, 6.1; SD, 4.3) than ADHD alone (M, 3.2; SD, 2.9; p ` .001. About 30% of the variance of impairment score of ADHD was explained by symptoms of ADHD and co-occurring symptoms of oppositional defiant disorder and conduct disorder. Few gender differences were observed. Conclusion: Overall, these non-referred young children with clinical symptoms of ADHD were only modestly impaired. Impairment related to ADHD occurred mainly in the areas of family functioning, and it was associated with ADHD subtype and comorbidity. Still, it is important to assess the impact of ADHD symptoms and coexisting difficulties among preschoolers to identify children and families who are in need of early intervention efforts.

Changes in the serum levels of brain-derived neurotrophic factor in adults with attention deficit hyperactivity disorder after treatment with atomoxetine

Atomoxetine (ATX) is a non-stimulant drug approved for the treatment of attention deficit hyperactivity disorder (ADHD). Although animal models have provided evidence that brain-derived neurotrophic factor (BDNF) is involved in the effects of ATX in the brain, there are no studies of BDNF in ADHD patients undergoing treatment with ATX. The aim of this study was to evaluate the possible changes in serum levels of BDNF in adults treated with ATX and its relationship with clinical improvement. A total of 54 adults with ADHD (age 33.43 ± 8.99years) without any medical or psychiatric comorbidities were treated with ATX for 3months; 35 of them completed the protocol. The clinical data for ADHD diagnosis, including Conners' ADHD Rating Scale and blood samples, were collected at baseline (V1) and at the end of the treatment (V2). Adults with ADHD who completed ATX treatment for 3months showed a significant improvement in their clinical symptoms. No significant differences were found in BDNF levels before and after treatment with ATX in the whole group of patients (p = 0.15). The inattentive subgroup of ATX responders showed a decrease of serum BDNF after 3months of ATX treatment (p = 0.05) not present in the combined subtype (p = 0.82). These results suggest that BDNF is not directly involved in the neurobiological mechanisms of ATX-induced improvement of clinical symptoms of ADHD. The differences between the combined and inattentive subtypes in serum BDNF changes suggest selective ATX-induced effects in the function of brain circuitry.

Local synchronization and amplitude of the fluctuation of spontaneous brain activity in attention-deficit/hyperactivity disorder: a resting-state fMRI study

Regional homogeneity (ReHo) and the amplitude of low-frequency fluctuation (ALFF) are two approaches to depicting different regional characteristics of resting-state functional magnetic resonance imaging (RS-fMRI) data. Whether they can complementarily reveal brain regional functional abnormalities in attention-deficit/hyperactivity disorder (ADHD) remains unknown. In this study, we applied ReHo and ALFF to 23 medication-naïve boys diagnosed with ADHD and 25 age-matched healthy male controls using whole-brain voxel-wise analysis. Correlation analyses were conducted in the ADHD group to investigate the relationship between the regional spontaneous brain activity measured by the two approaches and the clinical symptoms of ADHD. We found that the ReHo method showed widely-distributed differences between the two groups in the fronto-cingulo-occipito-cerebellar circuitry, while the ALFF method showed a difference only in the right occipital area. When a larger smoothing kernel and a more lenient threshold were used for ALFF, more overlapped regions were found between ALFF and ReHo, and ALFF even found some new regions with group differences. The ADHD symptom scores were correlated with the ReHo values in the right cerebellum, dorsal anterior cingulate cortex and left lingual gyrus in the ADHD group, while no correlation was detected between ALFF and ADHD symptoms. In conclusion, ReHo may be more sensitive to regional abnormalities, at least in boys with ADHD, than ALFF. And ALFF may be complementary to ReHo in measuring local spontaneous activity. Combination of the two may yield a more comprehensive pathophy-siological framework for ADHD.

Low dopamine D5 receptor density in hippocampus in an animal model of attention-deficit/hyperactivity disorder (ADHD)

A state of low dopaminergic activity has been implicated in attention-deficit/hyperactivity disorder (ADHD). The clinical symptoms of ADHD include inattention, impulsivity and hyperactivity, as well as impaired learning; dopaminergic modulation of the functions in the hippocampus is important to both learning and memory. To determine dopamine receptor (DR) density in a well-established animal model for ADHD, we quantified the dopamine D5 receptors in the hippocampus in the spontaneously hypertensive rat. We used immunofluorescence microscopy and immunogold electron microscopy to quantify the dopamine D5 receptor density on CA1 pyramidal cell somas and dendrites and dendritic spines in the stratum radiatum and stratum oriens. The density of the dopamine D5 receptors was significantly lower in the cytoplasm of pyramidal cell somas in the spontaneously hypertensive rat compared to the control, indicating a reduced reservoir for insertion of receptors into the plasma membrane. DRs are important for long-term potentiation and long-term depression, hence the deficit may contribute to the learning difficulties in individuals with the diagnosis of ADHD.